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SARS-CoV-2 belongs to the subgenus Sarbecovirus, which universally encodes the accessory protein ORF6. SARS-CoV-2 ORF6 is an antagonist of the interferon (IFN)-mediated antiviral response and plays an important role in viral infections. However, the mechanism by which the host counteracts the function of ORF6 to restrict viral replication remains unclear. In this study, we found that most ORF6 proteins encoded by sarbecoviruses could be ubiquitinated and subsequently degraded via the proteasome pathway. Through extensive screening, we identified that the deubiquitinase USP1, which effectively and broadly deubiquitinates sarbecovirus ORF6 proteins, stabilizes ORF6 proteins, resulting in enhanced viral replication. Therefore, ubiquitination and deubiquitination of ORF6 are important for antagonizing IFN-mediated antiviral signaling and influencing the virulence of SARS-CoV-2. These findings highlight an essential molecular mechanism and may provide a novel target for therapeutic interventions against viral infections.IMPORTANCEThe ORF6 proteins encoded by sarbecoviruses are essential for effective viral replication and infection and are important targets for developing effective intervention strategies. In this study, we confirmed that sarbecovirus ORF6 proteins are important antagonists of the host immune response and identified the regulatory mechanisms of ubiquitination and deubiquitination of most sarbecovirus ORF6 proteins. Moreover, we revealed that DUB USP1 prevents the proteasomal degradation of all ORF6 proteins, thereby promoting the virulence of SARS-CoV-2. Thus, impeding ORF6 function is helpful for attenuating the virulence of sarbecoviruses. Therefore, our findings provide a deeper understanding of the molecular mechanisms underlying sarbecovirus infections and offer potential new therapeutic targets for the prevention and treatment of these infections.
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SARS-CoV-2 , Proteínas Virales , Virosis , Humanos , Enzimas Desubicuitinizantes , Interferones/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/fisiología , Proteasas Ubiquitina-Específicas/genética , Proteasas Ubiquitina-Específicas/metabolismo , Proteínas Virales/genética , Proteínas Virales/metabolismoRESUMEN
BACKGROUND: In day-old Hungarian white goose goslings, there is a noticeable difference in dorsal down coloration between males and females, with females having darker dorsal plumage and males having lighter plumage. The ability to autosex day-old goslings based on their dorsal down coloration is important for managing them efficiently and planning their nutrition in the poultry industry. The aim of this study was to determine the biological and genetic factors underlying this difference in dorsal down colorationthrough histological analysis, biochemical assays, transcriptomic profiling, and qâPCR analysis. RESULTS: Tissue analysis and biochemical assays revealed that compared with males, 17-day-old embryos and day-old goslings of female geese exhibited a greater density of melanin-containing feather follicles and a greater melanin concentration in these follicles during development. Both female and male goslings had lower melanin concentrations in their dorsal skin compared to 17-day-old embryos. Transcriptome analysis identified a set of differentially expressed genes (DEGs) (MC1R, TYR, TYRP1, DCT and MITF) associated with melanogenesis pathways that were downregulated or silenced specifically in the dorsal skin of day-old goslings compared to 17-day-old embryos, affecting melanin synthesis in feather follicles. Additionally, two key genes (MC1R and MITF) associated with feather coloration showed differences between males and females, with females having higher expression levels correlated with increased melanin synthesis and darker plumage. CONCLUSION: The expression of multiple melanogenesis genes determines melanin synthesis in goose feather follicles. The dorsal down coloration of day-old Hungarian white goose goslings shows sexual dimorphism, likely due to differences in the expression of the MC1R and MITF genes between males and females. These results could help us better understand why male and female goslings exhibit different plumage patterns.
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Gansos , Perfilación de la Expresión Génica , Melaninas , Pigmentación , Caracteres Sexuales , Animales , Femenino , Masculino , Gansos/genética , Gansos/metabolismo , Melaninas/metabolismo , Pigmentación/genética , Plumas/metabolismo , Plumas/crecimiento & desarrollo , TranscriptomaRESUMEN
Aflatoxin B1 (AFB1) is commonly found in feed ingredients and foods all over the world, posing a significant threat to food safety and public health in animals and humans. Lactobacillus salivarius (L. salivarius) was recorded to improve the intestinal health and performance of chickens. However, whether L. salivarius can alleviate AFB1-induced hepatotoxicity in geese was unknown. A total of 300 Lande geese were randomly assigned to five groups: control group, AFB1 low-dose group (L), L. salivarius+AFB1 low-dose group (LL), AFB1 high dosage groups (H), L. salivarius+AFB1 high dosage groups (LH), respectively. The results showed that the concentrations of ALT, AST, and GGT significantly increased after exposure to AFB1. Similarly, severe damage of hepatic morphology was observed including the hepatic structure injury and inflammatory cell infiltration. The oxidative stress was evidenced by the elevated concentrations of MDA, and decreased activities of GSH-Px, GSH and SOD. The observation of immunofluorescence, real-time PCR, and western blotting showed that the expression of PINK1 and the value of LC3II/LC3I were increased, but that of p62 significantly decreased after AFB1 exposure. Moreover, the supplementation of L. salivarius effectively improved the geese performance, ameliorated AFB1-induced oxidative stress, inhibited mitochondrial mitophagy and enhanced the liver restoration to normal level. The present study demonstrated that L. salivarius ameliorated AFB1-induced the hepatotoxicity by decreasing the oxidative stress, and regulating the expression of PINK1/Parkin-mediated mitophagy in the mitochondria of the geese liver. Furthermore, this investigation suggested that L. salivarius might serve as a novel and safe additive for preventing AFB1 contamination in poultry feed.
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Aflatoxina B1 , Gansos , Ligilactobacillus salivarius , Hígado , Mitofagia , Proteínas Quinasas , Ubiquitina-Proteína Ligasas , Animales , Aflatoxina B1/toxicidad , Mitofagia/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Ligilactobacillus salivarius/fisiología , Hígado/efectos de los fármacos , Hígado/patología , Proteínas Quinasas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Estrés Oxidativo/efectos de los fármacos , Probióticos/farmacologíaRESUMEN
Unconsolidated porous media are distinct from consolidated porous rocks in the negligible bulk and shear moduli. This paper is motivated by resolving the control mechanism of P-wave attenuation in the media (represented by Toyoura sands and glass beads) saturated with water. The first model is Biot theory in which longitudinal friction (arising from velocity difference between the two phases) is quantified using dynamic permeability as a function of frequency. The first model simulates phase velocity (Vp) and the ultrasonically measured quality factor (Qp) well. A second model is the transverse squirt model in which squirt is induced by pressure differential between contact of grains (COG) and the main pore space. The second model outputs unrealistic Vp and Qp. The results reveal that P-wave attenuation in unconsolidated porous media (saturated with water) is governed by longitudinal friction rather than intrapore squirt. Remarkably, low-frequency dynamic permeability is much smaller than Darcy permeability, indicating that ultrasonic P-wave is surprisingly capable of indirectly detecting the very narrow gap at COG.
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This study aimed to investigate the role of the LCORL gene in regulating the growth performance of Zhedong white (ZDW) geese, belonging to the swan geese (Anser cygnoides), and identify possible selective signatures in diverse goose breeds. Single nucleotide polymorphisms around LCORL were genotyped, and their associations with body-size-related (BSR) traits were estimated. The results showed that the genotyped loci upstream of LCORL were significantly related to the body weight and breast width of ZDW geese aged 10 weeks (p < 0.05). A genome scan comparing expected heterozygosity among different breeds identified a ~150 kb long genomic region with extremely low heterozygosity downstream of LCORL among swan geese. Further, significant associations of variants within the low heterozygosity region among ZDW geese with BSR traits, including body weight, body length and breast width (p < 0.05) were also detected. Overall, mutations adjacent to LCORL were related to the growth performance of swan geese, and the significant effects of variants in a low-heterozygosity region on BSR traits provided valuable insights into the molecular mechanism of artificial selection reshaping body stature in swan geese.
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Gansos , Polimorfismo de Nucleótido Simple , Animales , Gansos/genética , Mutación , Peso Corporal/genéticaRESUMEN
Insulin-like growth factors 2 (IGF2) is an insulin-like growth factor that plays a major role in animal growth, cell proliferation and differentiation, as well as reproduction. IGF2 is well-known to be a candidate gene of growth and reproductive traits in many agricultural animals. Our previous study revealed that the G63A (Chr2: G26541617A) mutation within IGF2 exon 1 showed a significant association with egg numbers (E180d) of Sanhua goose population (p < 0.05). However, little work focus on the correlation between the IGF2 mutations and goose growth traits. In this study, qPCR indicated that the IGF2 mRNA highly expressed in leg muscle, liver, ovary and pituitary gland. Meanwhile, association analysis showed that the G63A mutation was significantly associated with the body weight of first-hatched Zhedong-White geese (BW0, p < 0.05), and strongly significantly associated with the BW2, BW4, BW6, BW8 and BW10 (p < 0.01). The GG homozygous had the lowest BW (from 4 weeks to 10 weeks) than those of AA and AG genotypes (p < 0.01), and the allele A was also positively correlated with the BW of the Zhedong-White goose population. Therefore, the G63A mutation in IGF2 may be an important genetic marker for goose breeding.
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Gansos , Femenino , Animales , Gansos/genética , Genotipo , Alelos , Fenotipo , MutaciónRESUMEN
Insulin-like growth factor 2 (IGF2) belongs to the member of the insulin-like growth factors family, which plays key roles in animal growth, differentiation and proliferation, as well as reproduction and the regulation of ovarian follicle development. However, little is known about the goose IGF2 gene. In this study, a 1879 bp fragment that covered the complete coding region (CDS) of goose IGF2 cDNA was identified for the first time. The cDNA consists of an open reading frame of 574 nucleotides with the capacity to encode a prepro-IGF-II protein of 187 amino acids, which comprises a signal peptide (24 residues), IGF-II peptide (67 residues), and C-terminal peptide (96 residues), and is closely related to that of chicken. qPCR indicates that the goose IGF2 mRNA is differentially expressed in all examined tissues of fertilized eggs (28 days) and laying Zhedong White geese (270 days). Two novel single nucleotide polymorphisms (SNPs) were detected in exon 1 (G63A, Chr2: G26541617A) and intron 1 (G38A, Chr2: G26541479A) regions, and the synonymous mutation G63A showed a significant association with egg numbers (E180d) of Sanhua goose population (p < 0.05). All the information derived from this study could be valuable and facilitate further studies on the functions of goose IGF2 gene.
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Gansos , Factor II del Crecimiento Similar a la Insulina , Femenino , Animales , Gansos/genética , Secuencia de Aminoácidos , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , ADN Complementario/genética , Polimorfismo de Nucleótido Simple/genética , Clonación MolecularRESUMEN
BACKGROUND: The evidence is sparse regarding the associations between serious mental illnesses (SMIs) prevalence and environmental factors in adulthood as well as the geographic distribution and variability of these associations. In this study, we evaluated the association between availability and proximity of green and blue space with SMI prevalence in England as a whole and in its major conurbations (Greater London, Birmingham, Liverpool and Manchester, Leeds, and Newcastle). METHODS AND FINDINGS: We carried out a retrospective analysis of routinely collected adult population (≥18 years) data at General Practitioner Practice (GPP) level. We used data from the Quality and Outcomes Framework (QOF) on the prevalence of a diagnosis of SMI (schizophrenia, bipolar affective disorder and other psychoses, and other patients on lithium therapy) at the level of GPP over the financial year April 2014 to March 2018. The number of GPPs included ranged between 7,492 (April 2017 to March 2018) to 7,997 (April 2014 to March 2015) and the number of patients ranged from 56,413,719 (April 2014 to March 2015) to 58,270,354 (April 2017 to March 2018). Data at GPP level were converted to the geographic hierarchy unit Lower Layer Super Output Area (LSOA) level for analysis. LSOAs are a geographic unit for reporting small area statistics and have an average population of around 1,500 people. We employed a Bayesian spatial regression model to explore the association of SMI prevalence in England and its major conurbations (greater London, Birmingham, Liverpool and Manchester, Leeds, and Newcastle) with environmental characteristics (green and blue space, flood risk areas, and air and noise pollution) and socioeconomic characteristics (age, ethnicity, and index of multiple deprivation (IMD)). We incorporated spatial random effects in our modelling to account for variation at multiple scales. Across England, the environmental characteristics associated with higher SMI prevalence at LSOA level were distance to public green space with a lake (prevalence ratio [95% credible interval]): 1.002 [1.001 to 1.003]), annual mean concentration of PM2.5 (1.014 [1.01 to 1.019]), and closeness to roads with noise levels above 75 dB (0.993 [0.992 to 0.995]). Higher SMI prevalence was also associated with a higher percentage of people above 24 years old (1.002 [1.002 to 1.003]), a higher percentage of ethnic minorities (1.002 [1.001 to 1.002]), and more deprived areas. Mean SMI prevalence at LSOA level in major conurbations mirrored the national associations with a few exceptions. In Birmingham, higher average SMI prevalence at LSOA level was positively associated with proximity to an urban green space with a lake (0.992 [0.99 to 0.998]). In Liverpool and Manchester, lower SMI prevalence was positively associated with road traffic noise ≥75 dB (1.012 [1.003 to 1.022]). In Birmingham, Liverpool, and Manchester, there was a positive association of SMI prevalence with distance to flood zone 3 (land within flood zone 3 has ≥1% chance of flooding annually from rivers or ≥0.5% chance of flooding annually from the sea, when flood defences are ignored): Birmingham: 1.012 [1.000 to 1.023]; Liverpool and Manchester: 1.016 [1.006 to 1.026]. In contrast, in Leeds, there was a negative association between SMI prevalence and distance to flood zone 3 (0.959 [0.944 to 0.975]). A limitation of this study was because we used a cross-sectional approach, we are unable to make causal inferences about our findings or investigate the temporal relationship between outcome and risk factors. Another limitation was that individuals who are exclusively treated under specialist mental health care and not seen in primary care at all were not included in this analysis. CONCLUSIONS: Our study provides further evidence on the significance of socioeconomic associations in patterns of SMI but emphasises the additional importance of considering environmental characteristics alongside socioeconomic variables in understanding these patterns. In this study, we did not observe a significant association between green space and SMI prevalence, but we did identify an apparent association between green spaces with a lake and SMI prevalence. Deprivation, higher concentrations of air pollution, and higher proportion of ethnic minorities were associated with higher SMI prevalence, supporting a social-ecological approach to public health prevention. It also provides evidence of the significance of spatial analysis in revealing the importance of place and context in influencing area-based patterns of SMI.
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Médicos Generales , Trastornos Mentales , Adulto , Teorema de Bayes , Inglaterra/epidemiología , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/epidemiología , Estudios Retrospectivos , Factores Socioeconómicos , Adulto JovenRESUMEN
Ubiquitination plays an important role in human immunodeficiency virus 1 (HIV-1) infection. HIV proteins such as Vif and Vpx mediate the degradation of the host proteins APOBEC3 and SAMHD1, respectively, through the proteasome pathway. However, whether deubiquitylating enzymes play an essential role in HIV-1 infection is largely unknown. Here, we demonstrate that the deubiquitinase USP21 potently inhibits HIV-1 production by indirectly downregulating the expression of HIV-1 transactivator of transcription (Tat), which is essential for transcriptional elongation in HIV-1. USP21 deubiquitylates Tat via its deubiquitinase activity, but a stronger ability to reduce Tat expression than a dominant-negative ubiquitin mutant (Ub-KO) showed that other mechanisms may contribute to USP21-mediated inhibition of Tat. Further investigation showed that USP21 downregulates cyclin T1 mRNA levels by increasing methylation of histone K9 in the promoter of cyclin T1, a subunit of the positive transcription elongation factor b (P-TEFb) that interacts with Tat and transactivation response element (TAR) and is required for transcription stimulation and Tat stability. Moreover, USP21 had no effect on the function of other HIV-1 accessory proteins, including Vif, Vpr, Vpx, and Vpu, indicating that USP21 was specific to Tat. These findings improve our understanding of USP21-mediated functional suppression of HIV-1 production. IMPORTANCE Ubiquitination plays an essential role in viral infection. Deubiquitinating enzymes (DUBs) reverse ubiquitination by cleaving ubiquitins from target proteins, thereby affecting viral infection. The role of the members of the USP family, which comprises the largest subfamily of DUBs, is largely unknown in HIV-1 infection. Here, we screened a series of USP members and found that USP21 inhibits HIV-1 production by specifically targeting Tat but not the other HIV-1 accessory proteins. Further investigations revealed that USP21 reduces Tat expression in two ways. First, USP21 deubiquitinates polyubiquitinated Tat, causing Tat instability, and second, USP21 reduces the mRNA levels of cyclin T1 (CycT1), an important component of P-TEFb, that leads to Tat downregulation. Thus, in this study, we report a novel role of the deubiquitinase, USP21, in HIV-1 infection. USP21 represents a potentially useful target for the development of novel anti-HIV drugs.
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Ciclina T/metabolismo , Enzimas Desubicuitinizantes/metabolismo , VIH-1/crecimiento & desarrollo , Ubiquitina Tiolesterasa/metabolismo , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/biosíntesis , Ciclina T/genética , Células HEK293 , Células HeLa , Histonas/metabolismo , Humanos , Células Jurkat , Regiones Promotoras Genéticas/genética , Biosíntesis de Proteínas/genética , ARN Mensajero/análisis , Replicación Viral/genéticaRESUMEN
We use the magnitude and centroid period of Rayleigh wave along with the amplitude of fluctuations of water level in a well to calculate effective porosity of a karst aquifer at the site scale. The radial and vertical displacements of Rayleigh wave are first related to the confining pressure of rock, which is then related to fluid pressure via the Gassmann equation. Three seismograms recorded at station 633A of the USARRAY and the induced responses of Well J-17 in the Edwards Aquifer (Texas) allow the calculation of an effective porosity between 17.0 and 24.4 percent, the average of which is close to the total porosity of core samples determined by geophysical well logs. This paper provides an innovative method to measure effective porosity in aquifers. Because of the long wavelengths of Rayleigh wave, the interdisciplinary approach is advantageous in that the resulting effective porosity is at the site scale which includes large conduits or voids.
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Long interspersed nuclear elements (LINE-1) is now considered as the only active autonomous mobile DNA in humans, LINE-1 retrotransposition activities are associated with and fluctuate during cancer initiation and progression; however, the mechanism underlying the increased LINE-1 activity in cancer is poorly understood. SAMHD1 has been reported to be a potent inhibitor of LINE-1 retrotransposition, and SAMHD1 mutations are frequently associated with cancer development. To gain insights on whether cancer-related SAMHD1 mutants affect LINE-1 activity, we explored the biochemical and cellular properties of some human mutants known correlate with the development of cancer. Most of the tested SAMHD1 cancer-related mutations were defective in LINE-1 inhibition. Interestingly we also found that SAMHD1 mutant K288T was defective for dNTPase activity but showed potent activity against LINE-1 retrotransposition. These findings suggest that LINE-1 inhibition does not depend solely on the dNTPase activity of SAMHD1. In contrast, SAMHD1's ability to inhibit ORF2p-mediated LINE-1 RNP reverse transcription was correlated with SAMHD1-mediated LINE-1 inhibition. Together, our data could also facilitate the deeper understanding for the inhibition of endogenous LINE-1 elements by SAMHD1.
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Elementos de Nucleótido Esparcido Largo/genética , Neoplasias/genética , Proteína 1 que Contiene Dominios SAM y HD/genética , Células Cultivadas , Células HEK293 , Humanos , Mutación , Proteínas Recombinantes/genéticaRESUMEN
BACKGROUND: Projections of future mortality and life expectancy are needed to plan for health and social services and pensions. Our aim was to forecast national age-specific mortality and life expectancy using an approach that takes into account the uncertainty related to the choice of forecasting model. METHODS: We developed an ensemble of 21 forecasting models, all of which probabilistically contributed towards the final projections. We applied this approach to project age-specific mortality to 2030 in 35 industrialised countries with high-quality vital statistics data. We used age-specific death rates to calculate life expectancy at birth and at age 65 years, and probability of dying before age 70 years, with life table methods. FINDINGS: Life expectancy is projected to increase in all 35 countries with a probability of at least 65% for women and 85% for men. There is a 90% probability that life expectancy at birth among South Korean women in 2030 will be higher than 86·7 years, the same as the highest worldwide life expectancy in 2012, and a 57% probability that it will be higher than 90 years. Projected female life expectancy in South Korea is followed by those in France, Spain, and Japan. There is a greater than 95% probability that life expectancy at birth among men in South Korea, Australia, and Switzerland will surpass 80 years in 2030, and a greater than 27% probability that it will surpass 85 years. Of the countries studied, the USA, Japan, Sweden, Greece, Macedonia, and Serbia have some of the lowest projected life expectancy gains for both men and women. The female life expectancy advantage over men is likely to shrink by 2030 in every country except Mexico, where female life expectancy is predicted to increase more than male life expectancy, and in Chile, France, and Greece where the two sexes will see similar gains. More than half of the projected gains in life expectancy at birth in women will be due to enhanced longevity above age 65 years. INTERPRETATION: There is more than a 50% probability that by 2030, national female life expectancy will break the 90 year barrier, a level that was deemed unattainable by some at the turn of the 21st century. Our projections show continued increases in longevity, and the need for careful planning for health and social services and pensions. FUNDING: UK Medical Research Council and US Environmental Protection Agency.
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Países Desarrollados/estadística & datos numéricos , Esperanza de Vida/tendencias , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Femenino , Predicción , Humanos , Tablas de Vida , MasculinoRESUMEN
BACKGROUND: To plan for pensions and health and social services, future mortality and life expectancy need to be forecast. Consistent forecasts for all subnational units within a country are very rare. Our aim was to forecast mortality and life expectancy for England and Wales' districts. METHODS: We developed Bayesian spatiotemporal models for forecasting of age-specific mortality and life expectancy at a local, small-area level. The models included components that accounted for mortality in relation to age, birth cohort, time, and space. We used geocoded mortality and population data between 1981 and 2012 from the Office for National Statistics together with the model with the smallest error to forecast age-specific death rates and life expectancy to 2030 for 375 of England and Wales' 376 districts. We measured model performance by withholding recent data and comparing forecasts with this withheld data. FINDINGS: Life expectancy at birth in England and Wales was 79·5 years (95% credible interval 79·5-79·6) for men and 83·3 years (83·3-83·4) for women in 2012. District life expectancies ranged between 75·2 years (74·9-75·6) and 83·4 years (82·1-84·8) for men and between 80·2 years (79·8-80·5) and 87·3 years (86·0-88·8) for women. Between 1981 and 2012, life expectancy increased by 8·2 years for men and 6·0 years for women, closing the female-male gap from 6·0 to 3·8 years. National life expectancy in 2030 is expected to reach 85·7 (84·2-87·4) years for men and 87·6 (86·7-88·9) years for women, further reducing the female advantage to 1·9 years. Life expectancy will reach or surpass 81·4 years for men and reach or surpass 84·5 years for women in every district by 2030. Longevity inequality across districts, measured as the difference between the 1st and 99th percentiles of district life expectancies, has risen since 1981, and is forecast to rise steadily to 8·3 years (6·8-9·7) for men and 8·3 years (7·1-9·4) for women by 2030. INTERPRETATION: Present forecasts underestimate the expected rise in life expectancy, especially for men, and hence the need to provide improved health and social services and pensions for elderly people in England and Wales. Health and social policies are needed to curb widening life expectancy inequalities, help deprived districts catch up in longevity gains, and avoid a so-called grand divergence in health and longevity. FUNDING: UK Medical Research Council and Public Health England.
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Esperanza de Vida/tendencias , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Inglaterra/epidemiología , Femenino , Mapeo Geográfico , Humanos , Masculino , Mortalidad/tendencias , Áreas de Pobreza , Factores Sexuales , Factores Socioeconómicos , Gales/epidemiologíaRESUMEN
Thermal asymmetric staggered PCR is the most widely used technique to obtain the flanking sequences. However, it has some limitations, including a low rate of positivity, and complex operation. In this study, a improved method of it was made based on suppression-PCR and touchdown PCR. The PCR fragment obtained by the amplification was used directly for sequencing after gel purification. Using this improved method, the positive rate of amplified flanking sequences of the ATMT mutants reached 99%. In addition, the time from DNA extraction to flanking sequence analysis was shortened to 2 days with about 6 dollars each sample.
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Agrobacterium tumefaciens/química , Aspergillus fumigatus/química , ADN Bacteriano/química , ADN de Hongos/química , Reacción en Cadena de la Polimerasa/métodos , Sporothrix/química , Agrobacterium tumefaciens/genética , Aspergillus fumigatus/genética , ADN Bacteriano/genética , ADN de Hongos/genética , Sporothrix/genéticaRESUMEN
To investigate the protective effects of oxymatrine (OMT) against H2O2-induced damage in L02 cells and research the mechanism,L02 cells were used as the research object. The oxidative stress model of L02 was established by hydrogen peroxide (H2O2). CCK-8 was used to detect the cell activation of L02 cells treated by different OMT. FCM (flow cytometry) assay was used to evaluate the cell proliferation of L02 cells treated by OMT. The apoptosis of L02 cells was detected using Annexin-V/7-AAD apoptosis detection kit. The level of ROS was detected by DCFH-DA fluorescence probe. The GSH-PX and SOD were detected by micro plate and colorimetric method. Results showed that when the concentration of OMT is between 6.25 and 100 mgâ¢L⻹, it could promote the production of NADPH and strengthen the activity of GSH-PX and SOD to get rid of the ROS to protect the L02 cell from the apoptosis of L02 cell induced by H2O2.
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Alcaloides/farmacología , Peróxido de Hidrógeno/efectos adversos , Estrés Oxidativo , Sustancias Protectoras/farmacología , Quinolizinas/farmacología , Apoptosis , Línea Celular , Fluoresceínas , HumanosRESUMEN
During the COVID-19 pandemic, studies in a number of countries have shown how wastewater can be used as an efficient surveillance tool to detect outbreaks at much lower cost than traditional prevalence surveys. In this study, we consider the utilisation of wastewater data in the post-pandemic setting, in which collection of health data via national randomised prevalence surveys will likely be run at a reduced scale; hence an affordable ongoing surveillance system will need to combine sparse prevalence data with non-traditional disease metrics such as wastewater measurements in order to estimate disease progression in a cost-effective manner. Here, we use data collected during the pandemic to model the dynamic relationship between spatially granular wastewater viral load and disease prevalence. We then use this relationship to nowcast local disease prevalence under the scenario that (i) spatially granular wastewater data continue to be collected; (ii) direct measurements of prevalence are only available at a coarser spatial resolution, for example at national or regional scale. The results from our cross-validation study demonstrate the added value of wastewater data in improving nowcast accuracy and reducing nowcast uncertainty. Our results also highlight the importance of incorporating prevalence data at a coarser spatial scale when nowcasting prevalence at fine spatial resolution, calling for the need to maintain some form of reduced-scale national prevalence surveys in non-epidemic periods. The model framework is disease-agnostic and could therefore be adapted to different diseases and incorporated into a multiplex surveillance system for early detection of emerging local outbreaks.
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COVID-19 , Humanos , COVID-19/epidemiología , Pandemias , Prevalencia , Aguas Residuales , BenchmarkingRESUMEN
Zongzi, made from glutinous rice, is usually thought to stay in the stomach for a long time, causing many people to shy away. In our research, Zongzi was prepared from three indica glutinous rice samples, and three japonica glutinous rice samples were digested in vitro in a human gastric simulator (HGS). It was found that digestion performance in HGS (gastric emptying) was mainly related to the hardness and stickiness of texture properties, and surprisingly, the hardness and stickiness of Zongzi were positively correlated, which contradicts past perception. Through the extraction and analysis of the coated layer on the surface of glutinous rice grains in Zongzi, the main source of its stickiness was the entanglement between the long chains of leached amylopectin molecules. The hardness was also mainly due to the high proportion of long chains in its glutinous rice starch, which made it difficult to gelatinize. Studies suggested that stickiness gradually disappeared during digestion, while hardness had a longer impact on digestive performance. The indica glutinous rice Zongzi with a higher long-chain level showed a higher resistant-starch (RS) level and slow hydrolysis in the intestinal digestion stage. Therefore, the texture and digestibility of Zongzi can be adjusted by changing the molecular structure of glutinous rice starch.
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Depression is a neurological disorder that profoundly affects human physical and mental health, resulting in various changes in the central nervous system. Despite several prominent hypotheses, such as the monoaminergic theory, hypothalamic-pituitary-adrenal (HPA) axis theory, neuroinflammation, and neuroplasticity, the current understanding of depression's pathogenesis remains incomplete. Importantly, depression is a gender-dimorphic disorder, with women exhibiting higher incidence rates than men. Given estrogen's pivotal role in the menstrual cycle, it is reasonable to postulate that its fluctuating levels could contribute to the pathogenesis of depression. Estrogen acts by binding to a diversity of receptors, which are widely distributed in the central nervous system. An abundance of research has established that estrogen and its receptors play a crucial role in depression, spanning pathogenesis and treatment. In this comprehensive review, we provide an in-depth analysis of the fundamental role of estrogen and its receptors in depression, with a focus on neuroinflammation, neuroendocrinology, and neuroplasticity. Furthermore, we discuss potential mechanisms underlying the therapeutic effects of estrogen in the treatment of depression, which may pave the way for new antidepressant drug development and alternative treatment options.
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Depresión , Enfermedades Neuroinflamatorias , Masculino , Femenino , Humanos , Depresión/tratamiento farmacológico , Estrógenos/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Antidepresivos/farmacología , Antidepresivos/uso terapéuticoRESUMEN
Aflatoxin B1 (AFB1) is a prevalent mycotoxin present in feed ingredients. In this study, we investigated the effects of Lactobacillus salivarius (L. salivarius) on the Landes geese exposed to AFB1. The 300 one-day-old Landes geese were randomly divided into five groups: The control group received a basic diet, while the other groups were fed a basic diet supplemented with 10 µg/kg AFB1, 10 µg/kg AFB1+ 4*108 cfu/g L. salivarius, 50 µg/kg AFB1, and 50 µg/kg AFB1 + 4*108 cfu/g L. salivarius for 63 d. Results showed that high level AFB1 exposure significantly decreased final BW and ADG, increased feed/gain ratio (F/G) and liver index (P < 0.05). L. salivarius improved levels of IL-1, IL-6, and IL-12 under low level of AFB1 exposure (P < 0.05), along with similar trends observed in serum IgA, IgG, IgM, T3, T4, TNF-É, and EDT (P < 0.05). AFB1 exposure reduced jejunum villus high and villus high/crypt depth ratio, and suppressed expression of ZO-1, Occludin, and Claudin-1 mRNA, and significant improved with L. salivarius supplementation under low level AFB1 exposure (P < 0.05). AFB1 significantly increased expression levels of TLR3 and NF-kB1, with supplementation of L. salivarius showing significant improvement under low AFB1 exposure (P < 0.05). Cecal microbiota sequencing revealed that under low level AFB1 exposure, supplementation with L. salivarius increased the abundance of Bacteroidetes and Lactococcus. In summary, supplementation with 4*108 cfu/g L. salivarius under 10 µg/kg AFB1 exposure improved growth performance and immune capacity, enhanced jejunum morphology, reduced liver inflammation, altered the cecal microbial structure, and positively affected the growth and development of geese.
Asunto(s)
Aflatoxina B1 , Alimentación Animal , Dieta , Gansos , Probióticos , Animales , Aflatoxina B1/toxicidad , Alimentación Animal/análisis , Probióticos/farmacología , Probióticos/administración & dosificación , Dieta/veterinaria , Ligilactobacillus salivarius/fisiología , Intestinos/efectos de los fármacos , Distribución Aleatoria , Suplementos Dietéticos/análisisRESUMEN
This study investigated the effects of partially replacing corn with elephant grass dry matter (air drass) on growth performance, serum parameters, carcass traits, and nutrient digestibility in geese. A total of 360 one-day-old Hortobágyi geese were randomly divided into three groups: control (basic diet), 12 % elephant grass, and 24 % elephant grass. The geese were raised for 70 days. The results showed that compared to the control, 12 % elephant grass had no adverse effects on final body weight, feed/gain ratio, mortality, serum liver and kidney function markers. However, 24 % elephant grass significantly reduced the final body weight (P < 0.001) and feed/gain ratio (P = 0.026) compared to the control group. Both experiment groups had decreased serum aspartate aminotransferase (P < 0.001), alanine aminotransferase (P < 0.001), alkaline phosphatase (P < 0.001), triglycerides (P < 0.001), and total cholesterol (P < 0.001). The addition of 12 % and 24 % elephant grass reduced abdominal fat (P = 0.002), but it had no significant effect on slaughter rate, half-bore rate, full-bore rate, breast muscle rate and leg muscle rate. For nutrient digestibility, 12 % elephant grass improved neutral detergent fiber digestibility compared to the control group (P = 0.026). The 24 % grass group had reduced Ca absorption (P = 0.020). Overall, the findings suggest that partially replacing corn with 12 % elephant grass in goose diet can maintain growth performance and carcass traits.It also has no negative effect on nutrient digestibility while improving serum parameters.